Gangliosides attenuate the delayed neurotoxicity of aspartic acid in vitro.
The neurotoxic effects of L-aspartate were evaluated in rat cerebellar granule cell cultures. Acute (15 min) exposure to L-aspartate produced a time-dependent, delayed degeneration of neuronal cell bodies and neurites (LD50 about 40 microM) over 24 h. Aspartate neurotoxicity was prevented by competitive and non-competitive N-methyl-D-aspartate (NMDA) antagonists, but not by non-NMDA antagonists, suggesting a major involvement of NMDA receptors in this neuronal injury. Gangliosides, including GM1, were also effective in attenuating the cytotoxicity of L-aspartate. The neurotoxic potential of L-aspartate may thus contribute to pathologies involving the action of endogenous excitatory amino acids.
Skaper
S D
SD
Fidia Research Laboratories, Department of CNS Research, Abano Terme, Italy.
Facci
L
L
Leon
A
A
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D007700:Kinetics; D015636:Magnesium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005732:Gangliosides; D015636:Magnesium Chloride; D001224:Aspartic Acid; D005677:G(M1) Ganglioside